The purpose of this project is to study the long-term health effects of therapeutic drugs as they may relate to carcinogenicity. Cohort studies of exposed groups are conducted, as well as case-control studies of selected cancer sites which involve lifetime drug use histories. Emphasis has been on the evaluation of various hormonal preparations, immunosuppressive drugs, and cancer chemotherapeutic agents. No general effects of thyroid medications or antihypertensive medications have been seen on breast cancer risk, but menopausal estrogens seem to increase the risk of benign breast disease. Ovarian cancer risk was found to be increased by use of progestins, but decreased by menopausal estrogen use. Cervical cancer was elevated among users of oral contraceptives, particularly for long-term users. Alkylating agents used for treatment of cancer and some non-neoplastic conditions were found to be associated with large excess risks of leukemia that were apparently dose related. Future analyses are planned to evaluate the effects of estrognic preparations on a variety of female tumors and to assess, systematically, the role of adjuvant drug therapy among patients treated for a number of different cancers.